The introduction of antiretroviral therapy (ART) in SSA has led to substantial improvements in morbidity and mortality in all age-groups except for adolescents and young adults (referred to as youth). In the HIV/AIDS Continuum of Care youth are particularly vulnerable to poor outcomes including loss from care, virologic failure, poor adherence with emergence of drug resistance. Effective proven strategies to improve outcomes are needed. Low cost objective measurements of adherence and drug resistance among youth are needed to help facilitate improved patient care and management. Measuring adherence in youth is challenging with unreliable metrics such as pill counts and/or self report or expensive electronic monitoring devices that are too costly and not practical for routine use. We propose to implement detection of tenofovir in hair and dried blood spots (DBS) as an objective measure of adherence. We will determine its accuracy for detecting non-adherence when compared with traditional measures such as pill counts, self-report, as well HIV viral load. The HIV genotype is useful for determining appropriate therapeutic regimens for individuals failing ART, however standard dideoxynucleotide sequencing (DDS or Sanger sequencing) is costly, and is often not available in much of SSA. We propose to implement a novel point mutation assay, to detect the most common mutations that arise from the use of first or second line therapies in SSA. The assay can be done on an RT- PCR platform and does not require expensive sequencing or specialized skills and bioinformatics tools for interpretation. We will evaluate the sensitivity an specificity of this assay when compared with standard sequencing. We propose to implement low-cost genotyping and novel strategies to determine adherence among youth who are failing ART. The study will occur within the context of evaluating a community-based program to strengthen adherence among youth failing ART within a public HIV/ART program. A cohort of 250 viremic youth (VL>1000 copies/mL) will be enrolled following informed consent and randomly assigned to the standard of care or to a community based intervention known as the Zvandiri program. Youth will be followed up for 48 weeks within the program at 12 week intervals, with plasma, dried blood spot and hair samples obtained at each interval visit. The Zvandiri intervention is ideal for testing these tools, as it will provide for a well characterized cohort with prospectively and purposefully collected samples. If successful the tools used can be rapidly scaled and implemented within a resource limited setting for genotyping and adherence assessments to guide management of youth living with HIV. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page